Our long-term goal is to understand the developmental and molecular basis for interactions that influence germline proliferation and differentiation. The germ cells of most animals, including mammals, proliferate extensively during development. This expansion is required to produce an adequate progenitor pool for adult gamete production. In addition to cell cycle progression, these cells must resist differentiation that would remove them from the proliferating state. We are investigating how nutritionally-sensitive signaling pathways control the accumulation and maintenance of the proliferating germ cells. These mechanisms are best studied in a whole-organism context that is amenable to genetic and molecular analysis, such as the nematode C. elegans. Recent studies from our lab implicate the highly conserved TOR target S6 kinase (S6K) in the control of germline proliferation and differentiation in C. elegans. Using complementary molecular-genetic and biochemical approaches, we propose to identify and characterize the relevant targets of S6K for its roles in regulating germline proliferation, differentiation, and sensitivity to organisal nutrition. Despite the evolutionary distance between C. elegans and mammals, this kinase is highly conserved. Therefore, these studies will likely provide broadly applicable results and lend insights into S6K function in other systems. Our studies will also shed light on general mechanisms that control the expansion of proliferating cell populations, with implications for fertility, development, cancer, and stem cell biology.